Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle

Qian Ouyang¹, Qiaoli Chen¹, Shunyuan Ke², Longfei Ding², Xinyu Yang², Ping Rong², Weikuan Feng², Ye Cao², Qi Wang², Min Li², Shu Su², Wen Wei², Minjun Liu², Jin Liu³, Xu Zhang³, John Zhong Li³, Hong-Yu Wang⁴, Shuai Chen⁵

Affiliations

¹ State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China; Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
² State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
³ The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Human Functional Genomics of Jiangsu Province, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China.
⁴ State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China; Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China. Electronic address: wanghy@nicemice.cn.
⁵ State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China; Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China. Electronic address: schen6@163.com.

PMID: 36800997
DOI: 10.1016/j.devcel.2023.01.007

Free article

Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle

Qian Ouyang et al. Dev Cell. 2023.

Free article

. 2023 Feb 27;58(4):289-305.e6.

doi: 10.1016/j.devcel.2023.01.007. Epub 2023 Feb 16.

Authors

Affiliations

¹ State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China; Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
² State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
³ The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Human Functional Genomics of Jiangsu Province, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China.
⁴ State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China; Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China. Electronic address: wanghy@nicemice.cn.
⁵ State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China; Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing 210061, China. Electronic address: schen6@163.com.

PMID: 36800997
DOI: 10.1016/j.devcel.2023.01.007

Abstract

Dynamic interaction between lipid droplets (LDs) and mitochondria controls the mobilization of long-chain fatty acids (LCFAs) from LDs for mitochondrial β-oxidation in skeletal muscle in response to energy stress. However, little is known about the composition and regulation of the tethering complex mediating LD-mitochondrion interaction. Here, we identify Rab8a as a mitochondrial receptor for LDs forming the tethering complex with the LD-associated PLIN5 in skeletal muscle. In rat L6 skeletal muscle cells, the energy sensor AMPK increases the GTP-bound active Rab8a that promotes LD-mitochondrion interaction through binding to PLIN5 upon starvation. The assembly of the Rab8a-PLIN5 tethering complex also recruits the adipose triglyceride lipase (ATGL), which couples LCFA mobilization from LDs with its transfer into mitochondria for β-oxidation. Rab8a deficiency impairs fatty acid utilization and decreases endurance during exercise in a mouse model. These findings may help to elucidate the regulatory mechanisms underlying the beneficial effects of exercise on lipid homeostasis control.

Keywords: AMPK; Rab8a; energy metabolism; exercise; fatty acid oxidation; lipid droplets; mitochondria; organelle interaction; skeletal muscle.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle

Affiliations

Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle

Authors

Affiliations

Abstract

Conflict of interest statement

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LinkOut - more resources

Full Text Sources

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